Mycobacteria are a genus of aerobic intracellular bacterial organisms that, upon infection of a host, survive within endosomal compartments of monocytes and macrophages. Human mycobacterial diseases include tuberculosis (caused by M. tuberculosis), leprosy (caused by M. leprae), Bairnsdale ulcers (caused by M. ulcerans), and various infections caused by M. marinum, M. kansasii, M. scrofulaceum, M. szulgai, M. xenopi, M. fortuitum, M. chelonei, M. haemophilum and M. intracellulare (see Wolinsky, E., Chapter 37 in Microbiology: Including Immunology and Molecular Genetics, 3rd Ed., Harper & Row, Philadelphia, 1980).
One third of the world's population harbors M. tuberculosis and is at risk for developing tuberculosis (TB). In immunocompromised patients, tuberculosis is increasing at a nearly logarithmic rate, and multidrug resistant strains are appearing. In addition, Mycobacterial strains which were previously considered to be nonpathogenic strains (e.g., M. avium) have now become major killers of immunosuppressed AIDS patients. Moreover, current Mycobacterial vaccines are either inadequate (such as the BCG vaccine for M. tuberculosis) or unavailable (such as for M. leprae) (Kaufmann, S., Microbiol. Sci. 4:324-328, 1987; U.S. Congress, Office of Technology Assessment, The Continuing Challenge of Tuberculosis, pp. 62-67, OTA-H-574, U.S. Government Printing Office, Washington, D.C., 1993).
The most distinctive cellular component of M. tuberculosis is its structurally atypical, functionally diverse, and physically robust cell envelope, which is widely held as an important contributor to the characteristic resilience of the pathogen (see, for example, Ehrt and Schnappinger, Cell Microbiol 11, 1170, 2009; Vandal et al., J Bacteriol 191, 625, 2009; Chatterjee, Curr Opin Chem Biol 1, 579, 1997; Brennan and Nikaido, Annu Rev Biochem 64, 29, 1995). The thick and waxy envelope presumably serves as physical barrier against antimycobacterial agents including antibiotics, as well as poses significant challenges in gaining physical access to its intracellular content for research and diagnostic purposes. There exists a need to identify an agent that could specifically recognize and destabilize M. tuberculosis cell envelope structure, such as to cause rapid but specific lysis of the pathogen. In addition, a need remains for methods for effective methods of detecting and treating a Mycobacterium infection, or for treating biofilms that contain the Mycobacterium, such as biofilms on indwelling medical devices.